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PubMed1977

A cytokinetic analysis of bacillus calmette-guérin-induced growth control of a murine leukemia.

The cytokinetics of an isogeneic, transplantable, lymphoid leukemia, growing as an ascitic tumor in the C57BL/6 mouse, has been investigated during normal growth and during regression induced by weekly injections i.v. of 1.0 mg Bacillus Calmette-Guérin (BCG). Survival was significantly prolonged in the BCG-treated group, and 27% of the mice were apparently cured. The tumor growth curves showed, furthermore, that BCG-rreated mice could be divided into two groups according to whether the ascitic tumor cell number was at control level or below that of the controls. By methods such as stathmokinetics, tritiated thymidine autoradiography, and cytophotometry, it was demonstrated that the proliferative activity was higher in BCG mice with a low tumor mass as compared to controls and BCG mice with a tumor mass similar to that of controls. The cytokinetic characteristics of BCG mice with a low ascitic tumor cell number were especially expressed by high mitotic activity, high initial labeling indices, short potential tumor doubling time, and a low number of G0-G1 cells. Furthermore the ascitic tumor cell loss rate was increased in these mice during the whole experimental period. It was deduced from the various parameters and especially from the cytophotometric and autoradiographic results that BCG induces a preferential kill of tumor cells in G0-G1 and the first part of the S phase. In addition, the cytological aspects of the ascitic tumor were found to be related to the cell kinetic pattern as the amount of small and large tumor cells increased and decreased, respectively, with accumulation of tumor cells in G0-G1.

Animals↗
PubMed1978

Resorption of bone implants. The effect of in vivo incorporation of a diphosphonate and fluoride on resorption.

Weanling isogenously related rats were divided into one control group, one group given a fluoride supplement of 100 parts/10(6) of F- in the drinking water, and a third group given 0.5 mg per kg body weight of phosphorus as dichloromethylene diphosphanic acid (Cl2MDP). The rats were labeled with 1 muCi per g body weight of 3H proline and 40 muCi of 45Ca. Four weeks after labeling, the animals were sacrificed and one scapula was implanted subcutaneously in the back of an isogenously related rat of the same age. The other scapula was stored in a freezer pending analysis. After another 4 weeks the implants were recovered and the radioactivity of each isotope was compared with that of the initially stored scapulae. A 30-40% loss of activity was found, reflecting a considerable loss of bone. However, this loss was significantly lower (P less than 0.01) when Cl2MDP was given to the donor animals, whereas fluoride treatment did not affect the resorption.

Animals↗
PubMedDate not supplied

Mouse tumour tests for quality control of C. parvum preparations.

Description of two mouse tumor tests selected to control the quality of C. parvum pilot productions: transplanted Ehrlich's ascitic tumor in inbred Swiss mice and transplanted YC8 ascitic tumor in isogenic Balb/c mice. The results obtained during three years of control are analyzed, particularly accuracy, long range adequacy and reproducibility of tumor challenges and C, parvum stimulations. The effects of some parameters of the tumor tests, e.g. dose-responses, treatment schedules, tumor-host relationships and standard preparations are discussed.

Animals↗
PubMed2026

Development of a human iPSC and patient phenotyping resource for preclinical investigations of neurodevelopmental disorders.

In this manuscript, we report the development of a comprehensive resource designed to harness the transformative potential of patient-derived induced pluripotent stem cells (iPSCs) to advance the study of neurodevelopmental disorders (NDDs). Using CRISPR-Cas-mediated genome editing, the Human Neuron Core generated a repository comprising 29 isogenic iPSC pairs, two sex-matched parental control iPSC pairs, and one unmatched patient line representing six monogenic NDDs: Tuberous Sclerosis Complex, PTEN Hamartoma Tumor Syndrome, KCNQ2 Developmental and Epileptic Encephalopathy, FOXG1 Syndrome, Phelan-McDermid Syndrome, and SETBP1 Haploinsufficiency Disorder. In parallel, detailed clinical phenotyping data were collected to enable comparison of cellular phenotypes with clinical severity in future studies. This integrated collection of genetically defined iPSC lines and associated clinical data provides a powerful platform for investigating disease mechanisms and advancing iPSC-based drug discovery for NDDs.

Humans↗
PubMed2025

A major trade-off between growth and defense in Arabidopsis thaliana can vanish in field conditions.

When wild plants defend themselves from pathogens, this often comes with a trade-off: the same genes that protect a plant from disease can also reduce its growth and fecundity in the absence of pathogens. One protein implicated in a major growth-defense trade-off is ACCELERATED CELL DEATH 6 (ACD6), an ion channel that modulates salicylic acid (SA) synthesis to potentiate a wide range of defenses. Wild Arabidopsis thaliana populations maintain significant functional variation at the ACD6 locus, with some alleles making the protein hyperactive. In the greenhouse, plants with hyperactive ACD6 alleles are resistant to diverse pathogens, yet they are of smaller stature, their leaves senesce earlier, and they set fewer seeds compared to plants with the standard allele. We hypothesized that ACD6 hyperactivity would not only affect the growth of microbial pathogens but also more generally change leaf microbiome assembly. To test this in an ecologically meaningful context, we compared plants with hyperactive, standard, and defective ACD6 alleles in the same field-collected soil, both outdoors and in naturally lit and climate-controlled indoor conditions, taking advantage of near-isogenic lines as well as a natural accession and a CRISPR-edited derivative. We surveyed visual phenotypes, gene expression, hormone levels, seed production, and the microbiome in each environment. The genetic precision of CRISPR-edited plants allowed us to conclude that ACD6 genotype had no effect on mature field plants in our setting, despite reproducibly dramatic effects on greenhouse plants. We conclude that additional abiotic and/or microbial signals present outdoors-but not in the greenhouse-greatly modulate ACD6 activity. This raises the possibility that the fitness costs of other commonly studied immune system genes may be grossly misjudged without field studies.

Arabidopsis↗
PubMed1979

[Characteristics of bacteriophage lambda and P1 modification-restriction in Escherichia coli strains controlled by factor R124].

The specifities of restriction of bacteriophages P1 and lambda controlled by R plasmids in Escherichia coli have been investigated. The isogenic strains harbouring the plasmids pAS26 coding for restriction endonuclease R.EcoRI, R245 coding for restriction endonuclease R.EcoRII and and R124 have been investigated in the present work. Modification-restriction controlled by R124 has been found to differ in specificity from those controlled by R245 and pAS26. Frequencies of restriction of bacteriophages P1vir and lambdavir specified by R124 pasmid differ from the frequencies in the strains harbouring pAS26 and R245 plasmids as well. The difference is due to the specifity of restriction-modification controlled by R124 plasmid. The data obtained are consistent with the determination of R124 specified restriction-modification activity as a novel one designated R.EcoRIII.

Anti-Bacterial Agents↗
PubMed1976

Mapping of two loci affecting the regulation of branched-chain amino acid transport in Escherichia coli K-12.

Two mutant loci resulting in derepression of, respectively, the L-leucine-specific transport system (lstR) and both the leucine-specific and the general branched-chain amino acid transport LIV-I systems (livR) were mapped by conjugation and transduction. Both livR and lstR were found to be closely linked to aroA at min 20 on the Escherichia coli genetic map. The merodiploid livR+/livR displayed wild-type regulation of L-leucine transport, indicating that the livR product is a diffusible, negative controlling element for high-affinity leucine transport systems. Isogenic strains carrying lstR, livR, and wild-type transport alleles were compared for leucine uptake kinetic parameters and leucine-binding protein levels. The higher levels of leucine transport in the mutant strains under repressing conditions were generally due to increased high-affinity systems, which were accompanied by striking increases in the level of leucine-binding proteins.

Biological Transport, Active↗
PubMed1976

A transcriptional barrier in the regulatory region of the tryptophan operon of Escherichia coli: its role in the regulation of repressor-independent RNA synthesis.

A study was made of the influence of the growth rate of Escherichia coli bacteria on the transcription of the tryptophan (trp) operon, in various trp repressor negative strains. Selective measurement of the levels of RNA transcribed from the regulatory region (reg) of this operon and from the structural genes, respectively, has revealed that the increase of the rate of trpRNA synthesis with bacterial growth rate (Rose and Yanofsky, 1972) is due to a decrease of the frequency of termination of transcription at the transcriptional barrier in the regulatory region of the operon. In a mutant strain of E. coli with a deletion covering the promotor distal part of the regulatory region of the trp operon where the barrier is located, the rate of trpRNA synthesis is not affected by the growth rate. In suA- strains, in which Rho factor activity is reduced the bacterial growth rate does not affect the rate of synthesis of trpRNA. This result suggests that in wild type bacteria Rho factor contributes to the control of the transcription of the trp operon. In bacteria with a mutation rendering Tryptophanyl-tRNA synthetase (TRSase) inactive (trpS- strains) the rate of trpRNA synthesis is affected by the growth rate in the same way as in the isogenic wild type bacteria. This result indicates that TRSase plays no obligatory role in the control of trpRNA synthesis through a mechanism of termination and anti-termination of transcription, at least not in the studied strains, which carried a relA mutation.

Binding, Competitive↗
PubMed1978

Neonatal islet cell transplantation in the diabetic rat: effect on the renal complications.

PVG/C rats were made diabetic with streptozotocin and after 1 mth received a single intraperitoneal transplant of isogeneic collagenase digested pancreatic tissue. Renal changes have been studied in transplanted and control diabetic rats using light and electron microscopy and immunological techniques. Following transplantation, renal lesions did not increase in severity and progressive basement membrane thickening was prevented. Ultrastructurally many glomeruli showed a significant reduction in the mesangial matrix and the tubular and mesangial cell changes reverted to normal. Immunofluorescent studies demonstrated a similar reduction in the glomerular deposits of IgG. Possibilities for the treatment of diabetes mellitus in human patients are discussed.

Animals↗
PubMed1978

[Research on the artificial regulation of sex in animals in the USSR].

The problem of artificial sex control was cardinally solved only for the silkworm among the domestic animals. The artificial sex control is realized by means of several methods. The artificial ameiotic parthenogenesis allows to obtain isogenic parthenogenetic progeny of only female sex. The meiotic parthenogenesis, on the contrary, gives only male progeny characterized by homozygosis by all genes. As a result of androgenesis with the participation of ooplasm and male nuclear material, only male progeny develops as well. Sex marked strains in which the female and male eggs are coloured in different may were obtained by means of translocation of the dominant genes controlling the egg colour on W chromosome determining the female sex. This allows readily to pick out the eggs of desirable sex only with the help of photoelectric equipment. The males of a specially raised strain balanced by two non-allelic sex-linked lethals, when being crossed with the females of any other strain, give male progeny only. The developed methods of sex control have found wide application in theoretical investigations of various directions and practical sericulture.

Animals↗
PubMed1977

Behavioral differences among isogenic strains of Drosophila mercatorum.

Mating propensity in eight all-female laboratory lines was measured. The lines are completely isogenic, but each has a different past history. In all cases, mating propensity was significantly lower than in the bisexual controls; in some cases, mating speed was less by a factor of 10. Three of the four lines deriving from the same wild strain are not only different from the parent strain but also different from each other. A highly significant difference exists between two strains recently obtained by selection for parthenogenesis from the same natural population. One strain appears to produce a substance which reduces mating propensity of control females if females from the two strains are reared together in the same vial. As none of the strains was behaviorally selected prior to testing, these behaviors appear to be incidental accompaniments of the very powerful isogenizing effect of the genetic system in these parthenogenetic strains. Indeed, the data show that partial isolation from sexual reproduction can arise wholly by chance. This may have some relevance to theories of species origin which are accompanied by a strong initial founder effect.

Animals↗
PubMed1979

Thymic involvement in control of bone marrow growth. Use of T-cell-depleted hybrid mice.

Because of mounting evidence of involvement of thymus-derived cells in blood formation we have studied the growth of transplanted bone marrow in mice extensively depleted of T-lymphocytes (TCD). Poor growth of parental marrow was found not to be appreciably altered in TCD hybrid recipients. However, parental thymic lymphocytes even in massive doses were not able to augment hemopoiesis in TCD hosts, in contrast to findings from sham-thymectomized or age control mice. This indication that a third (host) cell takes part in the thymocyte-marrow stem cell interaction was reinforced by the finding that isogenic (hybrid) thymocytes administered to TCD mice 5 weeks before the final irradiation restored their ability to support thymocyte-induced augmentation of parental marrow growth. Data were obtained from theta-poor sham-thymectomized irradiated controls which are interpreted as evidence for a suppressor T cell. Thymocytes administered with marrow produced a shift toward granulopoiesis in TCD mice as well as in controls. From this finding we infer that although thymus-derived cells are intimately involved in regulation of myelopoiesis, the effect of administered thymic lymphocytes on the differentiative pathway does not depend on host T cells.

Animals↗
PubMed1976

[Antitumoral immunity induced by the administration of homologous and isologous tumoral cells treated by moderate heating].

Treatment of tumour cells with heat ranging between 46 and 52 degrees C attenuates strongly their virulence and renders the tumour cells immunogenic to the host. By repeated administration of heat treated tumour cells suspended in Freund's complete adjuvant, the animals acquire a state of immunity which makes them tolerant to tumour inocula 100% lethal in the controls. The immunity so conferred is cell-mediated and can be adoptively transferred to isogenic recipients with donor peritoneal exudate and, to a lesser degree, splenic cells.

Animals↗
PubMed1977

Isolation of a lambdadcys transducing bacteriophage and its use in determining the regulation of cysteine messenger ribonucleic acid synthesis in Escherichia coli K-12.

A defective specialized lambda transducing phage carrying the cysJ, cysI, cysH, and cysD genes has been isolated from a secondary-site lysogen. Deoxyribonucleic acid-ribonucleic acid (DNA-RNA) hybridization studies utilizing this phage have been carried out to detect cysteine-specific messenger RNA (cys mRNA) synthesized in vivo. A vivo. A 3.5- to 9-fold increase in the rate of synthesis of cys mRNA has been detected in the derepressed wild-type (Cys+) strain grown on glutathione compared with a repressed control grown on cystine. Pleiotropic cysE and cysB mutants grown on glutathione were found to possess rates of synthesis of cys mRNA that were significantly lower than their derepressed isogenic parent. The addition of O-acetyl-L-serine to the cysE strain produced a 5.5-fold increase in the rate of synthesis of cys mRNA. These results indicate that cysteine biosynthesis is controlled at the level of transcription by the inducer O-acetylserine, the cysB protein and cyst(e)ine.

Bacterial Proteins↗
PubMed1977

Clinical effect of allopurinol on preserved kidneys: a randomized double-blind study.

We investigated the clinical posttransplant effect of allopurinol on preserved kidneys. Thirty-four paired kidneys from brain-dead cadavers were preserved by hypothermic pulsatile perfusion with silica gel fraction in separate cassettes. Allopurinol was added to one perfusate and omitted from the other in a randomized, double-blind, prospective plan. There was no difference in the short-term or long-term function of either group of kidneys. Allopurinol does not appear to have as consistent a beneficial effect on non-ischemically damaged human kidneys as that observed experimentally on ischemically damaged canine organs.

Adult↗
PubMed1977

Cellular and humoral immunity to leukemia cells in BCG-induced growth control of a murine leukemia.

The antitumor effects of weekly iv injections of 1.0 mg BCG and/or sc injections of 10(7) irradiated leukemia cells were studied in an isogeneic, transplantable lymphoid leukemia in the C57BL/6 mouse. The injections were started at day 1 after ip inoculation of 10(5) leukemia cells. BCG prolonged the survival time of most animals and cured 22%. BCG plus irradiated cells cured only about 10% of the mice, and irradiated cells alone had no curative effect. Individual tumor-bearing mice in the various experimental groups were examined with respect to ascites tumor cell number; complement-dependent cytotoxic antibodies in sera; direct and antibody-dependent cytotoxicity to tumor cells of lymphoid cells from peritoneal fluid, the spleen, and peripheral lymph nodes; and the cytology of ascites, the spleen, and lymph nodes. Only the antibody-dependent lymphocyte-mediated cytotoxicity (ADLMC) was correlated with the ascites tumor cell number, since the ADLMC was high only in mice with a tumor cell number less than that of the controls. Furthermore, since mice with a low tumor cell number had predominantly only lymphocytes as the nonmalignant cell type in their peritoneal fluid, ADLMC may have had an important role in BCG-induced control of tumor growth.

Animals↗
PubMed2026

Narasin used as a feed additive in conventional rearing of broilers can co-select for vancomycin-resistant Enterococcus faecium through the NarAB ionophore resistance mechanisms.

OBJECTIVES: To investigate the role of the NarAB resistance mechanism in the selection of vancomycin-resistant Enterococcus faecium (VREfm) and assess the impact of ionophore feed additives, particularly narasin, on the emergence of VREfm in broiler chickens. MATERIALS AND METHODS: Three isogenic E. faecium strains with different antimicrobial resistance determinants were created by mutagenesis and conjugation and used in a controlled animal experiment. Ross 308 broiler chickens were inoculated with either a rifampicin-resistant, a rifampicin- and vancomycin-resistant or a rifampicin-, vancomycin- and narasin-resistant strain and fed diets supplemented with selected ionophores. Bacterial populations were analysed on selective Slanetz and Bartley agar to determine the presence and selection of VREfm and other vancomycin-resistant species. Bacterial inoculation strains and isolates were whole genome sequenced for species identification and to identify genetic resistance mechanisms. RESULTS: Narasin was shown to select for VREfm in broilers, with NarAB being essential for co-selection. Intrinsically vancomycin-resistant Pediococcus acidilactici and Enterococcus gallinarum were identified as part of the broilers' vancomycin-resistant resident microbiota. Notably, among the P. acidilactici isolates that were susceptibility tested, strains resistant to both vancomycin and narasin were only found in broilers fed narasin, supporting that narasin promotes the growth of narasin-resistant populations. CONCLUSION: Narasin use in broiler feed can co-select for vancomycin-resistant bacteria, including VREfm, through the NarAB mechanism. These findings emphasize the concerns associated with the use of particular ionophores in poultry and suggest that vancomycin and narasin resistance may be more widespread in the broiler microbiota than previously recognized. Further research is needed to understand the implications for antimicrobial resistance and human health.

Animals↗